ID CP2E1_HUMAN Reviewed; 493 AA. AC P05181; Q5VZD5; Q6NWT9; Q9UK47; DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot. DT 01-APR-1988, sequence version 1. DT 27-MAR-2024, entry version 225. DE RecName: Full=Cytochrome P450 2E1 {ECO:0000303|PubMed:8031147}; DE EC=1.14.14.1 {ECO:0000269|PubMed:10553002, ECO:0000269|PubMed:18577768}; DE AltName: Full=4-nitrophenol 2-hydroxylase; DE EC=1.14.13.n7 {ECO:0000269|PubMed:9348445}; DE AltName: Full=CYPIIE1; DE AltName: Full=Cytochrome P450-J; GN Name=CYP2E1 {ECO:0000303|PubMed:10553002, ECO:0000312|HGNC:HGNC:2631}; GN Synonyms=CYP2E; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=3782137; DOI=10.1016/s0021-9258(18)66620-7; RA Song B.-J., Gelboin H.V., Park S.-S., Yang C.S., Gonzalez F.J.; RT "Complementary DNA and protein sequences of ethanol-inducible rat and human RT cytochrome P-450s. Transcriptional and post-transcriptional regulation of RT the rat enzyme."; RL J. Biol. Chem. 261:16689-16697(1986). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=3233219; DOI=10.1021/bi00425a019; RA Umeno M., McBride O.W., Yang C.S., Gelboin H.V., Gonzalez F.J.; RT "Human ethanol-inducible P450IIE1: complete gene sequence, promoter RT characterization, chromosome mapping, and cDNA-directed expression."; RL Biochemistry 27:9006-9013(1988). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Liver; RA Zhuge J., Qian Y., Xie H., Yu Y.; RT "Sequence of a new human cytochrome P450-2E1 cDNA and establishing the RT transgenic cell line."; RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ASP-219; CYS-366 AND RP LEU-457. RG NIEHS SNPs program; RL Submitted (APR-2006) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164054; DOI=10.1038/nature02462; RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P., RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 10."; RL Nature 429:375-381(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 32-493. RC TISSUE=Brain; RA Yoo M., Shin S.W.; RT "Partial sequence of human brain cytochrome P450 2E1."; RL Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 387-432. RA Iwahashi K., Okuyama E., Nakamura K., Furukawa A., Ichikawa Y.; RT "Rapid detection of a novel mutation in the human CYP2EI exon VIII by the RT PCR method."; RL Submitted (APR-1995) to the EMBL/GenBank/DDBJ databases. RN [10] RP PROTEIN SEQUENCE OF 1-20. RC TISSUE=Liver; RX PubMed=3675576; DOI=10.1016/0006-291x(87)91100-4; RA Lasker J.M., Raucy J., Kubota S., Bloswick B.P., Black M., Lieber C.S.; RT "Purification and characterization of human liver cytochrome P-450-ALC."; RL Biochem. Biophys. Res. Commun. 148:232-238(1987). RN [11] RP PROTEIN SEQUENCE OF 3-20. RX PubMed=2587619; DOI=10.1159/000138590; RA Robinson R.C., Shorr R.G., Varrichio A., Park S.S., Gelboin H.V., RA Miller H., Friedman F.K.; RT "Human liver cytochrome P-450 related to a rat acetone-inducible, RT nitrosamine-metabolizing cytochrome P-450: identification and isolation."; RL Pharmacology 39:137-144(1989). RN [12] RP PROTEIN SEQUENCE OF 23-42. RX PubMed=8031147; DOI=10.1006/abbi.1994.1280; RA Gillam E.M., Guo Z., Guengerich F.P.; RT "Expression of modified human cytochrome P450 2E1 in Escherichia coli, RT purification, and spectral and catalytic properties."; RL Arch. Biochem. Biophys. 312:59-66(1994). RN [13] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=9348445; DOI=10.1021/tx970048z; RA Zerilli A., Ratanasavanh D., Lucas D., Goasduff T., Dreano Y., Menard C., RA Picart D., Berthou F.; RT "Both cytochromes P450 2E1 and 3A are involved in the O-hydroxylation of p- RT nitrophenol, a catalytic activity known to be specific for P450 2E1."; RL Chem. Res. Toxicol. 10:1205-1212(1997). RN [14] RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND ACTIVITY REGULATION. RX PubMed=10553002; RA Adas F., Salauen J.P., Berthou F., Picart D., Simon B., Amet Y.; RT "Requirement for omega and (omega;-1)-hydroxylations of fatty acids by RT human cytochromes P450 2E1 and 4A11."; RL J. Lipid Res. 40:1990-1997(1999). RN [15] RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY. RX PubMed=18577768; DOI=10.1194/jlr.m800199-jlr200; RA Fer M., Corcos L., Dreano Y., Plee-Gautier E., Salaun J.P., Berthou F., RA Amet Y.; RT "Cytochromes P450 from family 4 are the main omega hydroxylating enzymes in RT humans: CYP4F3B is the prominent player in PUFA metabolism."; RL J. Lipid Res. 49:2379-2389(2008). RN [16] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [17] RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 32-493 IN COMPLEX WITH THE RP INHIBITORS INDAZOLE AND 4-METHYLPYRAZOLE AND HEME. RX PubMed=18818195; DOI=10.1074/jbc.m805999200; RA Porubsky P.R., Meneely K.M., Scott E.E.; RT "Structures of human cytochrome P-450 2E1. Insights into the binding of RT inhibitors and both small molecular weight and fatty acid substrates."; RL J. Biol. Chem. 283:33698-33707(2008). RN [18] RP VARIANTS HIS-76 AND ILE-389. RX PubMed=9058590; RA Hu Y., Oscarson M., Johansson I., Yue Q.Y., Dahl M.L., Tabone M., RA Arinco S., Albano E., Ingelman-Sundberg M.; RT "Genetic polymorphism of human CYP2E1: characterization of two variant RT alleles."; RL Mol. Pharmacol. 51:370-376(1997). RN [19] RP VARIANT ILE-179. RX PubMed=9918138; DOI=10.1097/00008571-199812000-00011; RA Fairbrother K.S., Grove J., de Waziers I., Steimel D.T., Day C.P., RA Crespi C.L., Daly A.K.; RT "Detection and characterization of novel polymorphisms in the CYP2E1 RT gene."; RL Pharmacogenetics 8:543-552(1998). RN [20] RP VARIANTS ILE-179 AND LEU-457. RX PubMed=15469410; DOI=10.1517/14622416.5.7.895; RA Solus J.F., Arietta B.J., Harris J.R., Sexton D.P., Steward J.Q., RA McMunn C., Ihrie P., Mehall J.M., Edwards T.L., Dawson E.P.; RT "Genetic variation in eleven phase I drug metabolism genes in an ethnically RT diverse population."; RL Pharmacogenomics 5:895-931(2004). CC -!- FUNCTION: A cytochrome P450 monooxygenase involved in the metabolism of CC fatty acids (PubMed:10553002, PubMed:18577768). Mechanistically, uses CC molecular oxygen inserting one oxygen atom into a substrate, and CC reducing the second into a water molecule, with two electrons provided CC by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) CC (PubMed:10553002, PubMed:18577768). Catalyzes the hydroxylation of CC carbon-hydrogen bonds. Hydroxylates fatty acids specifically at the CC omega-1 position displaying the highest catalytic activity for CC saturated fatty acids (PubMed:10553002, PubMed:18577768). May be CC involved in the oxidative metabolism of xenobiotics (Probable). CC {ECO:0000269|PubMed:10553002, ECO:0000269|PubMed:18577768, CC ECO:0000305|PubMed:9348445}. CC -!- CATALYTIC ACTIVITY: CC Reaction=an organic molecule + O2 + reduced [NADPH--hemoprotein CC reductase] = an alcohol + H(+) + H2O + oxidized [NADPH--hemoprotein CC reductase]; Xref=Rhea:RHEA:17149, Rhea:RHEA-COMP:11964, Rhea:RHEA- CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:30879, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, CC ChEBI:CHEBI:142491; EC=1.14.14.1; CC Evidence={ECO:0000269|PubMed:10553002, ECO:0000269|PubMed:18577768}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17150; CC Evidence={ECO:0000305|PubMed:10553002, ECO:0000305|PubMed:18577768}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(5Z,8Z,11Z)-eicosatrienoate + O2 + reduced [NADPH--hemoprotein CC reductase] = 19-hydroxy-(5Z,8Z,11Z)-eicosatrienoate + H(+) + H2O + CC oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:50076, CC Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, CC ChEBI:CHEBI:58210, ChEBI:CHEBI:78043, ChEBI:CHEBI:132024; CC Evidence={ECO:0000269|PubMed:18577768}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50077; CC Evidence={ECO:0000305|PubMed:18577768}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + O2 + reduced CC [NADPH--hemoprotein reductase] = 19-hydroxy-(5Z,8Z,11Z,14Z,17Z)- CC eicosapentaenoate + H(+) + H2O + oxidized [NADPH--hemoprotein CC reductase]; Xref=Rhea:RHEA:39787, Rhea:RHEA-COMP:11964, Rhea:RHEA- CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:58562, CC ChEBI:CHEBI:76636; Evidence={ECO:0000269|PubMed:18577768}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39788; CC Evidence={ECO:0000305|PubMed:18577768}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 + reduced CC [NADPH--hemoprotein reductase] = 21-hydroxy-(4Z,7Z,10Z,13Z,16Z,19Z)- CC docosahexaenoate + H(+) + H2O + oxidized [NADPH--hemoprotein CC reductase]; Xref=Rhea:RHEA:50088, Rhea:RHEA-COMP:11964, Rhea:RHEA- CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:77016, CC ChEBI:CHEBI:132025; Evidence={ECO:0000269|PubMed:18577768}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50089; CC Evidence={ECO:0000305|PubMed:18577768}; CC -!- CATALYTIC ACTIVITY: CC Reaction=dodecanoate + O2 + reduced [NADPH--hemoprotein reductase] = CC 11-hydroxydodecanoate + H(+) + H2O + oxidized [NADPH--hemoprotein CC reductase]; Xref=Rhea:RHEA:39751, Rhea:RHEA-COMP:11964, Rhea:RHEA- CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:18262, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, CC ChEBI:CHEBI:76628; Evidence={ECO:0000269|PubMed:10553002}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39752; CC Evidence={ECO:0000305|PubMed:10553002}; CC -!- CATALYTIC ACTIVITY: CC Reaction=O2 + reduced [NADPH--hemoprotein reductase] + tetradecanoate = CC 13-hydroxytetradecanoate + H(+) + H2O + oxidized [NADPH--hemoprotein CC reductase]; Xref=Rhea:RHEA:50096, Rhea:RHEA-COMP:11964, Rhea:RHEA- CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:30807, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, CC ChEBI:CHEBI:132031; Evidence={ECO:0000269|PubMed:10553002}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50097; CC Evidence={ECO:0000305|PubMed:10553002}; CC -!- CATALYTIC ACTIVITY: CC Reaction=4-nitrophenol + H(+) + NADPH + O2 = 4-nitrocatechol + H2O + CC NADP(+); Xref=Rhea:RHEA:26205, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:15379, ChEBI:CHEBI:57730, ChEBI:CHEBI:57783, CC ChEBI:CHEBI:57917, ChEBI:CHEBI:58349; EC=1.14.13.n7; CC Evidence={ECO:0000269|PubMed:9348445}; CC -!- COFACTOR: CC Name=heme; Xref=ChEBI:CHEBI:30413; CC -!- ACTIVITY REGULATION: The omega-1 hydroxylase activity is stimulated by CC cytochrome b5. {ECO:0000269|PubMed:10553002}. CC -!- PATHWAY: Lipid metabolism; fatty acid metabolism. CC {ECO:0000269|PubMed:10553002, ECO:0000269|PubMed:18577768}. CC -!- SUBUNIT: Interacts with chaperones HSP70 and HSP90; this interaction is CC required for initial targeting to mitochondria. CC {ECO:0000250|UniProtKB:P05182}. CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000250|UniProtKB:P05182}; Peripheral membrane protein CC {ECO:0000250|UniProtKB:P05182}. Microsome membrane CC {ECO:0000250|UniProtKB:P05182}; Peripheral membrane protein CC {ECO:0000250|UniProtKB:P05182}. Mitochondrion inner membrane CC {ECO:0000250|UniProtKB:P05182}; Peripheral membrane protein CC {ECO:0000250|UniProtKB:P05182}. Note=Post-translationally targeted to CC mitochondria. TOMM70 is required for the translocation across the CC mitochondrial outer membrane. After translocation into the matrix, CC associates with the inner membrane as a membrane extrinsic protein. CC {ECO:0000250|UniProtKB:P05182}. CC -!- INDUCTION: By ethanol and isoniazid. CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=PharmVar Pharmacogen Variation Consortium; CC Note=CYP2E1 alleles; CC URL="https://www.pharmvar.org/gene/CYP2E1"; CC -!- WEB RESOURCE: Name=Wikipedia; Note=CYP2E1 entry; CC URL="https://en.wikipedia.org/wiki/CYP2E1"; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/cyp2e1/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; J02625; AAA35743.1; -; mRNA. DR EMBL; J02843; AAA52155.1; -; Genomic_DNA. DR EMBL; AF182276; AAF13601.1; -; mRNA. DR EMBL; DQ515958; ABF47105.1; -; Genomic_DNA. DR EMBL; AL161645; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471211; EAW61357.1; -; Genomic_DNA. DR EMBL; BC067433; AAH67433.1; -; mRNA. DR EMBL; AF084225; AAD13753.1; -; mRNA. DR EMBL; D50111; BAA08796.1; -; Genomic_DNA. DR CCDS; CCDS7686.1; -. DR PIR; A31949; A31949. DR RefSeq; NP_000764.1; NM_000773.3. DR PDB; 3E4E; X-ray; 2.60 A; A/B=32-493. DR PDB; 3E6I; X-ray; 2.20 A; A/B=32-493. DR PDB; 3GPH; X-ray; 2.70 A; A/B=32-493. DR PDB; 3KOH; X-ray; 2.90 A; A/B=32-493. DR PDB; 3LC4; X-ray; 3.10 A; A/B=32-493. DR PDB; 3T3Z; X-ray; 2.35 A; A/B/C/D=32-493. DR PDBsum; 3E4E; -. DR PDBsum; 3E6I; -. DR PDBsum; 3GPH; -. DR PDBsum; 3KOH; -. DR PDBsum; 3LC4; -. DR PDBsum; 3T3Z; -. DR AlphaFoldDB; P05181; -. DR SMR; P05181; -. DR BioGRID; 107944; 20. DR IntAct; P05181; 12. DR STRING; 9606.ENSP00000440689; -. DR BindingDB; P05181; -. DR ChEMBL; CHEMBL5281; -. DR DrugBank; DB13963; 1,2-dichlorobenzene. DR DrugBank; DB00316; Acetaminophen. DR DrugBank; DB00118; Ademetionine. DR DrugBank; DB00041; Aldesleukin. DR DrugBank; DB00918; Almotriptan. DR DrugBank; DB00969; Alosetron. DR DrugBank; DB01223; Aminophylline. DR DrugBank; DB06728; Aniline. DR DrugBank; DB01435; Antipyrine. DR DrugBank; DB00972; Azelastine. DR DrugBank; DB01086; Benzocaine. DR DrugBank; DB06770; Benzyl alcohol. DR DrugBank; DB04794; Bifonazole. DR DrugBank; DB01558; Bromazepam. DR DrugBank; DB01156; Bupropion. DR DrugBank; DB00201; Caffeine. DR DrugBank; DB09061; Cannabidiol. DR DrugBank; DB14737; Cannabinol. DR DrugBank; DB06774; Capsaicin. DR DrugBank; DB06016; Cariprazine. DR DrugBank; DB01136; Carvedilol. DR DrugBank; DB06119; Cenobamate. DR DrugBank; DB00477; Chlorpromazine. DR DrugBank; DB00356; Chlorzoxazone. DR DrugBank; DB00501; Cimetidine. DR DrugBank; DB12499; Clascoterone. DR DrugBank; DB04920; Clevidipine. DR DrugBank; DB00636; Clofibrate. DR DrugBank; DB01068; Clonazepam. DR DrugBank; DB00257; Clotrimazole. DR DrugBank; DB01394; Colchicine. DR DrugBank; DB00851; Dacarbazine. DR DrugBank; DB06637; Dalfampridine. DR DrugBank; DB00250; Dapsone. DR DrugBank; DB11943; Delafloxacin. DR DrugBank; DB01189; Desflurane. DR DrugBank; DB01151; Desipramine. DR DrugBank; DB01234; Dexamethasone. DR DrugBank; DB14649; Dexamethasone acetate. DR DrugBank; DB01191; Dexfenfluramine. DR DrugBank; DB04856; Dexloxiglumide. DR DrugBank; DB00633; Dexmedetomidine. DR DrugBank; DB11994; Diacerein. DR DrugBank; DB14046; Dichlorobenzene. DR DrugBank; DB00586; Diclofenac. DR DrugBank; DB00255; Diethylstilbestrol. DR DrugBank; DB08995; Diosmin. DR DrugBank; DB00822; Disulfiram. DR DrugBank; DB02520; Ditiocarb. DR DrugBank; DB00869; Dorzolamide. DR DrugBank; DB01127; Econazole. DR DrugBank; DB08846; Ellagic acid. DR DrugBank; DB00228; Enflurane. DR DrugBank; DB00109; Enfuvirtide. DR DrugBank; DB00655; Estrone. DR DrugBank; DB00330; Ethambutol. DR DrugBank; DB00898; Ethanol. DR DrugBank; DB00593; Ethosuximide. DR DrugBank; DB00773; Etoposide. DR DrugBank; DB01628; Etoricoxib. DR DrugBank; DB12466; Favipiravir. DR DrugBank; DB00949; Felbamate. DR DrugBank; DB08868; Fingolimod. DR DrugBank; DB01544; Flunitrazepam. DR DrugBank; DB00623; Fluphenazine. DR DrugBank; DB00690; Flurazepam. DR DrugBank; DB01213; Fomepizole. DR DrugBank; DB09462; Glycerin. DR DrugBank; DB05708; GTS-21. DR DrugBank; DB01159; Halothane. DR DrugBank; DB04946; Iloperidone. DR DrugBank; DB00458; Imipramine. DR DrugBank; DB06370; Indisulam. DR DrugBank; DB00753; Isoflurane. DR DrugBank; DB00951; Isoniazid. DR DrugBank; DB00883; Isosorbide dinitrate. DR DrugBank; DB01167; Itraconazole. DR DrugBank; DB00602; Ivermectin. DR DrugBank; DB06448; Lonafarnib. DR DrugBank; DB14009; Medical Cannabis. DR DrugBank; DB00170; Menadione. DR DrugBank; DB00763; Methimazole. DR DrugBank; DB01403; Methotrimeprazine. DR DrugBank; DB01028; Methoxyflurane. DR DrugBank; DB01011; Metyrapone. DR DrugBank; DB00379; Mexiletine. DR DrugBank; DB01110; Miconazole. DR DrugBank; DB06595; Midostaurin. DR DrugBank; DB01204; Mitoxantrone. DR DrugBank; DB01844; N,N-dimethylformamide. DR DrugBank; DB04379; N-Methyl-N-(Methylbenzyl)Formamide. DR DrugBank; DB00486; Nabilone. DR DrugBank; DB00627; Niacin. DR DrugBank; DB00622; Nicardipine. DR DrugBank; DB02701; Nicotinamide. DR DrugBank; DB00184; Nicotine. DR DrugBank; DB01115; Nifedipine. DR DrugBank; DB06712; Nilvadipine. DR DrugBank; DB01595; Nitrazepam. DR DrugBank; DB00540; Nortriptyline. DR DrugBank; DB00904; Ondansetron. DR DrugBank; DB01173; Orphenadrine. DR DrugBank; DB11837; Osilodrostat. DR DrugBank; DB00617; Paramethadione. DR DrugBank; DB03783; Phenacetin. DR DrugBank; DB00780; Phenelzine. DR DrugBank; DB01174; Phenobarbital. DR DrugBank; DB00252; Phenytoin. DR DrugBank; DB13941; Piperaquine. DR DrugBank; DB04951; Pirfenidone. DR DrugBank; DB04977; Plitidepsin. DR DrugBank; DB00794; Primidone. DR DrugBank; DB09288; Propacetamol. DR DrugBank; DB00818; Propofol. DR DrugBank; DB04216; Quercetin. DR DrugBank; DB00908; Quinidine. DR DrugBank; DB00468; Quinine. DR DrugBank; DB13174; Rhein. DR DrugBank; DB01045; Rifampicin. DR DrugBank; DB08864; Rilpivirine. DR DrugBank; DB14840; Ripretinib. DR DrugBank; DB00412; Rosiglitazone. DR DrugBank; DB06201; Rufinamide. DR DrugBank; DB11689; Selumetinib. DR DrugBank; DB01104; Sertraline. DR DrugBank; DB01236; Sevoflurane. DR DrugBank; DB00203; Sildenafil. DR DrugBank; DB00428; Streptozocin. DR DrugBank; DB00675; Tamoxifen. DR DrugBank; DB09256; Tegafur. DR DrugBank; DB01079; Tegaserod. DR DrugBank; DB01412; Theobromine. DR DrugBank; DB00277; Theophylline. DR DrugBank; DB01154; Thiamylal. DR DrugBank; DB00679; Thioridazine. DR DrugBank; DB00208; Ticlopidine. DR DrugBank; DB01007; Tioconazole. DR DrugBank; DB04858; Tirapazamine. DR DrugBank; DB05109; Trabectedin. DR DrugBank; DB00347; Trimethadione. DR DrugBank; DB13609; Umifenovir. DR DrugBank; DB09328; Vayarin. DR DrugBank; DB00661; Verapamil. DR DrugBank; DB09120; Zucapsaicin. DR DrugCentral; P05181; -. DR GuidetoPHARMACOLOGY; 1330; -. DR SwissLipids; SLP:000001596; -. DR iPTMnet; P05181; -. DR PhosphoSitePlus; P05181; -. DR BioMuta; CYP2E1; -. DR DMDM; 117250; -. DR MassIVE; P05181; -. DR PaxDb; 9606-ENSP00000440689; -. DR PeptideAtlas; P05181; -. DR ProteomicsDB; 51820; -. DR Antibodypedia; 2427; 765 antibodies from 39 providers. DR DNASU; 1571; -. DR Ensembl; ENST00000252945.8; ENSP00000252945.3; ENSG00000130649.10. DR Ensembl; ENST00000463117.6; ENSP00000440689.1; ENSG00000130649.10. DR GeneID; 1571; -. DR KEGG; hsa:1571; -. DR MANE-Select; ENST00000252945.8; ENSP00000252945.3; NM_000773.4; NP_000764.1. DR UCSC; uc001lnj.1; human. DR AGR; HGNC:2631; -. DR CTD; 1571; -. DR DisGeNET; 1571; -. DR GeneCards; CYP2E1; -. DR HGNC; HGNC:2631; CYP2E1. DR HPA; ENSG00000130649; Tissue enriched (liver). DR MIM; 124040; gene. DR neXtProt; NX_P05181; -. DR OpenTargets; ENSG00000130649; -. DR PharmGKB; PA129; -. DR VEuPathDB; HostDB:ENSG00000130649; -. DR eggNOG; KOG0156; Eukaryota. DR GeneTree; ENSGT00940000161594; -. DR HOGENOM; CLU_001570_22_3_1; -. DR InParanoid; P05181; -. DR OMA; LMYGRRI; -. DR OrthoDB; 2900138at2759; -. DR PhylomeDB; P05181; -. DR TreeFam; TF352043; -. DR BioCyc; MetaCyc:HS05414-MONOMER; -. DR PathwayCommons; P05181; -. DR Reactome; R-HSA-211981; Xenobiotics. DR Reactome; R-HSA-211999; CYP2E1 reactions. DR Reactome; R-HSA-9027307; Biosynthesis of maresin-like SPMs. DR Reactome; R-HSA-9749641; Aspirin ADME. DR Reactome; R-HSA-9753281; Paracetamol ADME. DR SABIO-RK; P05181; -. DR SignaLink; P05181; -. DR SIGNOR; P05181; -. DR UniPathway; UPA00199; -. DR BioGRID-ORCS; 1571; 8 hits in 1144 CRISPR screens. DR ChiTaRS; CYP2E1; human. DR EvolutionaryTrace; P05181; -. DR GeneWiki; CYP2E1; -. DR GenomeRNAi; 1571; -. DR Pharos; P05181; Tchem. DR PRO; PR:P05181; -. DR Proteomes; UP000005640; Chromosome 10. DR RNAct; P05181; Protein. DR Bgee; ENSG00000130649; Expressed in right lobe of liver and 151 other cell types or tissues. DR ExpressionAtlas; P05181; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central. DR GO; GO:0005743; C:mitochondrial inner membrane; ISS:UniProtKB. DR GO; GO:0018601; F:4-nitrophenol 2-monooxygenase activity; IDA:UniProtKB. DR GO; GO:0008392; F:arachidonic acid epoxygenase activity; IBA:GO_Central. DR GO; GO:0070330; F:aromatase activity; IEA:UniProtKB-EC. DR GO; GO:0019899; F:enzyme binding; IPI:BHF-UCL. DR GO; GO:0020037; F:heme binding; IDA:UniProtKB. DR GO; GO:0030544; F:Hsp70 protein binding; ISS:UniProtKB. DR GO; GO:0051879; F:Hsp90 protein binding; ISS:UniProtKB. DR GO; GO:0005506; F:iron ion binding; IEA:InterPro. DR GO; GO:0120319; F:long-chain fatty acid omega-1 hydroxylase activity; IDA:UniProtKB. DR GO; GO:0004497; F:monooxygenase activity; IDA:UniProtKB. DR GO; GO:0016491; F:oxidoreductase activity; IDA:BHF-UCL. DR GO; GO:0016709; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen; TAS:UniProtKB. DR GO; GO:0016712; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen; IBA:GO_Central. DR GO; GO:0019825; F:oxygen binding; TAS:ProtInc. DR GO; GO:0018960; P:4-nitrophenol metabolic process; IDA:UniProtKB. DR GO; GO:0018910; P:benzene metabolic process; TAS:Reactome. DR GO; GO:0018885; P:carbon tetrachloride metabolic process; TAS:Reactome. DR GO; GO:0019373; P:epoxygenase P450 pathway; IBA:GO_Central. DR GO; GO:0042197; P:halogenated hydrocarbon metabolic process; TAS:Reactome. DR GO; GO:0046483; P:heterocycle metabolic process; IDA:BHF-UCL. DR GO; GO:0002933; P:lipid hydroxylation; IDA:UniProtKB. DR GO; GO:0042759; P:long-chain fatty acid biosynthetic process; TAS:Reactome. DR GO; GO:0001676; P:long-chain fatty acid metabolic process; IDA:UniProtKB. DR GO; GO:0016098; P:monoterpenoid metabolic process; IDA:BHF-UCL. DR GO; GO:0009617; P:response to bacterium; IEA:Ensembl. DR GO; GO:0008202; P:steroid metabolic process; IMP:BHF-UCL. DR GO; GO:0006805; P:xenobiotic metabolic process; IDA:BHF-UCL. DR CDD; cd20665; CYP2C-like; 1. DR Gene3D; 1.10.630.10; Cytochrome P450; 1. DR InterPro; IPR001128; Cyt_P450. DR InterPro; IPR017972; Cyt_P450_CS. DR InterPro; IPR002401; Cyt_P450_E_grp-I. DR InterPro; IPR008070; Cyt_P450_E_grp-I_CYP2E-like. DR InterPro; IPR036396; Cyt_P450_sf. DR PANTHER; PTHR24300:SF356; CYTOCHROME P450 2E1; 1. DR PANTHER; PTHR24300; CYTOCHROME P450 508A4-RELATED; 1. DR Pfam; PF00067; p450; 1. DR PRINTS; PR00463; EP450I. DR PRINTS; PR01687; EP450ICYP2E. DR PRINTS; PR00385; P450. DR SUPFAM; SSF48264; Cytochrome P450; 1. DR PROSITE; PS00086; CYTOCHROME_P450; 1. DR Genevisible; P05181; HS. PE 1: Evidence at protein level; KW 3D-structure; Direct protein sequencing; Endoplasmic reticulum; KW Fatty acid metabolism; Heme; Iron; Lipid metabolism; Membrane; KW Metal-binding; Microsome; Mitochondrion; Mitochondrion inner membrane; KW Monooxygenase; NADP; Oxidoreductase; Reference proteome. FT CHAIN 1..493 FT /note="Cytochrome P450 2E1" FT /id="PRO_0000051751" FT BINDING 298..303 FT /ligand="substrate" FT /evidence="ECO:0000305" FT BINDING 437 FT /ligand="heme" FT /ligand_id="ChEBI:CHEBI:30413" FT /ligand_part="Fe" FT /ligand_part_id="ChEBI:CHEBI:18248" FT /note="axial binding residue" FT VARIANT 76 FT /note="R -> H (in allele CYP2E1*2; reduced activity; FT dbSNP:rs72559710)" FT /evidence="ECO:0000269|PubMed:9058590" FT /id="VAR_008360" FT VARIANT 179 FT /note="V -> I (in allele CYP2E1*4; dbSNP:rs6413419)" FT /evidence="ECO:0000269|PubMed:15469410, FT ECO:0000269|PubMed:9918138" FT /id="VAR_008361" FT VARIANT 219 FT /note="N -> D (in dbSNP:rs41299426)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_055382" FT VARIANT 366 FT /note="S -> C (in dbSNP:rs41299434)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_055383" FT VARIANT 389 FT /note="V -> I (in allele CYP2E1*3; dbSNP:rs55897648)" FT /evidence="ECO:0000269|PubMed:9058590" FT /id="VAR_008362" FT VARIANT 457 FT /note="H -> L (in dbSNP:rs28969387)" FT /evidence="ECO:0000269|PubMed:15469410, ECO:0000269|Ref.4" FT /id="VAR_024727" FT CONFLICT 2 FT /note="Missing (in Ref. 10; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 23 FT /note="W -> A (in Ref. 12; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 32 FT /note="L -> N (in Ref. 12; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 71 FT /note="Y -> C (in Ref. 7; AAH67433)" FT /evidence="ECO:0000305" FT CONFLICT 235 FT /note="V -> A (in Ref. 3; AAF13601)" FT /evidence="ECO:0000305" FT CONFLICT 355 FT /note="H -> R (in Ref. 7; AAH67433)" FT /evidence="ECO:0000305" FT TURN 40..42 FT /evidence="ECO:0007829|PDB:3E6I" FT HELIX 45..47 FT /evidence="ECO:0007829|PDB:3E6I" FT HELIX 50..52 FT /evidence="ECO:0007829|PDB:3T3Z" FT HELIX 53..64 FT /evidence="ECO:0007829|PDB:3E6I" FT STRAND 66..72 FT /evidence="ECO:0007829|PDB:3E6I" FT STRAND 75..80 FT /evidence="ECO:0007829|PDB:3E6I" FT HELIX 83..91 FT /evidence="ECO:0007829|PDB:3E6I" FT TURN 94..97 FT /evidence="ECO:0007829|PDB:3E6I" FT HELIX 104..109 FT /evidence="ECO:0007829|PDB:3E6I" FT STRAND 112..114 FT /evidence="ECO:0007829|PDB:3E6I" FT HELIX 122..135 FT /evidence="ECO:0007829|PDB:3E6I" FT HELIX 142..159 FT /evidence="ECO:0007829|PDB:3E6I" FT TURN 160..163 FT /evidence="ECO:0007829|PDB:3E6I" FT HELIX 169..172 FT /evidence="ECO:0007829|PDB:3E6I" FT HELIX 174..185 FT /evidence="ECO:0007829|PDB:3E6I" FT HELIX 194..209 FT /evidence="ECO:0007829|PDB:3E6I" FT HELIX 213..220 FT /evidence="ECO:0007829|PDB:3E6I" FT HELIX 222..225 FT /evidence="ECO:0007829|PDB:3E6I" FT STRAND 228..230 FT /evidence="ECO:0007829|PDB:3T3Z" FT HELIX 231..255 FT /evidence="ECO:0007829|PDB:3E6I" FT STRAND 259..261 FT /evidence="ECO:0007829|PDB:3KOH" FT HELIX 265..274 FT /evidence="ECO:0007829|PDB:3E6I" FT STRAND 275..278 FT /evidence="ECO:0007829|PDB:3E6I" FT STRAND 279..281 FT /evidence="ECO:0007829|PDB:3T3Z" FT HELIX 286..317 FT /evidence="ECO:0007829|PDB:3E6I" FT HELIX 319..332 FT /evidence="ECO:0007829|PDB:3E6I" FT TURN 333..336 FT /evidence="ECO:0007829|PDB:3E6I" FT HELIX 341..346 FT /evidence="ECO:0007829|PDB:3E6I" FT HELIX 348..361 FT /evidence="ECO:0007829|PDB:3E6I" FT STRAND 376..378 FT /evidence="ECO:0007829|PDB:3E6I" FT STRAND 381..383 FT /evidence="ECO:0007829|PDB:3E6I" FT STRAND 388..391 FT /evidence="ECO:0007829|PDB:3E6I" FT HELIX 394..397 FT /evidence="ECO:0007829|PDB:3E6I" FT TURN 400..402 FT /evidence="ECO:0007829|PDB:3E6I" FT STRAND 403..405 FT /evidence="ECO:0007829|PDB:3E6I" FT HELIX 411..414 FT /evidence="ECO:0007829|PDB:3E6I" FT STRAND 419..421 FT /evidence="ECO:0007829|PDB:3E6I" FT HELIX 433..435 FT /evidence="ECO:0007829|PDB:3LC4" FT HELIX 440..457 FT /evidence="ECO:0007829|PDB:3E6I" FT STRAND 458..464 FT /evidence="ECO:0007829|PDB:3E6I" FT TURN 466..468 FT /evidence="ECO:0007829|PDB:3E6I" FT STRAND 474..481 FT /evidence="ECO:0007829|PDB:3E6I" FT STRAND 487..491 FT /evidence="ECO:0007829|PDB:3E6I" SQ SEQUENCE 493 AA; 56849 MW; ED0399E32A005644 CRC64; MSALGVTVAL LVWAAFLLLV SMWRQVHSSW NLPPGPFPLP IIGNLFQLEL KNIPKSFTRL AQRFGPVFTL YVGSQRMVVM HGYKAVKEAL LDYKDEFSGR GDLPAFHAHR DRGIIFNNGP TWKDIRRFSL TTLRNYGMGK QGNESRIQRE AHFLLEALRK TQGQPFDPTF LIGCAPCNVI ADILFRKHFD YNDEKFLRLM YLFNENFHLL STPWLQLYNN FPSFLHYLPG SHRKVIKNVA EVKEYVSERV KEHHQSLDPN CPRDLTDCLL VEMEKEKHSA ERLYTMDGIT VTVADLFFAG TETTSTTLRY GLLILMKYPE IEEKLHEEID RVIGPSRIPA IKDRQEMPYM DAVVHEIQRF ITLVPSNLPH EATRDTIFRG YLIPKGTVVV PTLDSVLYDN QEFPDPEKFK PEHFLNENGK FKYSDYFKPF STGKRVCAGE GLARMELFLL LCAILQHFNL KPLVDPKDID LSPIHIGFGC IPPRYKLCVI PRS //